Many of the investigations in this genetic epidemiology project arise from observations in families at high risk of cancer or in other etiologic studies. Analyses of the data from the survey of the Jewish population in the metropolitan D.C. area continued. Risks of second cancers following breast cancer were assessed. The risk of contralateral breast cancer was not significantly higher among mutation carriers compared to noncarriers. Risk of a second ovary cancer, however, was higher. Retrospective review of cranial CT studies in 56 patients with medulloblastoma and 159 emergency room controls revealed that 9% of medulloblastoma patients without shunts, 16% with shunts, and 10% of emergency room controls had falx calcification. Only the two patients with both medulloblastoma and the nevoid basal cell carcinoma syndrome, however, demonstrated falx calcification in the peridiagnostic period. Among individuals with Beckwith-Wiedemann syndrome, approximately 25% have nonmalignant renal abnormalities including medullary renal cysts, caliceal diverticula, hydronephrosis and nephrolithiasis. As a follow-up to a just completed DCEG comprehensive case-control study of adults with brain tumors, a family-based study of the parents, siblings and adult children of the 480 eligible glioma cases is being conducted. Relatives will be interviewed about personal and family medical history and other risk factors and will be asked to provide buccal cells as a source of DNA. The relatives will be used as controls for the glioma cases in association studies and in analyses to evaluate the roles of genetic susceptibility and environmental exposures on the risk of gliomas and etiologically related tumors. Epidemiologic and genetic approaches for examining gene-environment interaction were reviewed. Traditional epidemiologic approaches have sufficient power to detect interaction in studies of common genetic and/or environmental factors. Studies of rare factors, however, will likely require alternative study designs such as multi-stage sampling, countermatching or case-case designs.